Objective: To evaluate whether bilateral DBS lead placement asymmetry captures clinically meaningful correlates of motor outcomes, particularly freezing of gait (FoG) and balance to establish a feasibility pipeline before validation on real patient data.

Background: Post-DBS clinical response may not be explained solely by global motor scores, and lead asymmetry may be relevant for axial outcomes  However, its contribution to  axial symptom response remains insufficiently characterized.

Method: A synthetic pilot cohort was generated to model DBS-related asymmetry using demographic, clinical, and stimulation-linked variables, including bilateral lead coordinates, amplitude, and volume of tissue activated (VTA-)-derived asymmetry indices. Additionally, an auxiliary physiology cohort (n=30) incorporated STN-related markers, including mean spontaneous firing rate, (MSFR), beta oscillatory activity, and tremor-frequency neuronal patterns.

Derived variables included medio-lateral lead asymmetry (abs_dx),amplitude asymmetry, and VTA asymmetry. Associations were tested using Spearman correlation, and predictive models were evaluated using leave-one-out cross-validation to estimate their ability to identify FoG responders.

Results: (: abs_dx) showed a significant association with FoG improvement (rho = -0.4902, p =< 0.001) and balance improvement measured by Berg score change (rho = -0.4009, p = <0.001) but not with overall motor or lateral clinical asymmetry. VTA asymmetry alone did not show significant correlations with FoG or balance outcomes. 

Among predictive models, FoG regression achieved R²=0.71 (MAE = 2.0333, ), and FoG responder classification reached balanced accuracy of 0.79. Berg regression was moderately informative, while lateral asymmetry models were weak. In the auxiliary physiology cohort, MSFR and beta-related markers were positively associated with rigidity/bradykinesia measures, and tremor-frequency neuronal activity correlated with tremor-related scores, providing biological plausibility for symptom-specific modeling approaches.

Conclusion: This synthetic feasibility study suggests that DBS lead asymmetry can capture clinically relevant signal primarily in axial outcomes, especially FoG  These results highlight the potential relevance of spatial lead asymmetry  and provide a framework for subsequent validation in real-world clinical datasets.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lead-asymmetry-and-axial-symptom-response-to-deep-brain-stimulation-in-parkinsons-disease-a-synthetic-pilot-modeling-study/